5294-61-1

Basic information

• Product Name: N-(2,6-Diphenylmethyl)-1-piperazine acetylamine
• Synonyms: 1-[(2,6-DIMETHYLANILINO)CARBONYL-METHYL]-PIPERAZINE;N-(2,6-DIMETHYLPHENYL)-1-PIPERAZIN-ACETAMIDE;N-(2,6-DIMETHYLPHENYL)-1-PIPERAZINEACETAMIDE;N-(2,6-DIMETHYL-PHENYL)-2-PIPERAZIN-1-YL-ACETAMIDE;N-(2,6-Diphenylmethyl)-1-piperazine acetylamine;1-[N-(2,6-dimethylphenyl)carbamoylmethyl]piperazine;RZ-2;1-(2,6-Dimethylphenyl)-1-Piperazineacetamide
• CAS NO: 5294-61-1
• Molecular Formula: C₁₄H₂₁N₃O
• Molecular Weight: 247.34
• EINECS: 1806241-263-5
• Product Categories: INTERMEDIATESOFRANOLAZINE;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Ranolazine
• Mol File: 5294-61-1.mol
• Article Data: 21

Chemical Properties

• Melting Point: 110-112°C
• Boiling Point: 411.2 °C at760mmHg
• Flash Point: 202.5 °C
• Appearance: Light gray/Crystalline Powder
• Density: 1.101±0.06 g/cm3(Predicted)
• Vapor Pressure: 5.7E-07mmHg at 25°C
• Storage Temp.: -20°C Freezer
• Solubility: DMSO, Methanol
• PKA: 14.62±0.70(Predicted)
• CAS DataBase Reference: N-(2,6-Diphenylmethyl)-1-piperazine acetylamine(CAS DataBase Reference)
• NIST Chemistry Reference: N-(2,6-Diphenylmethyl)-1-piperazine acetylamine(5294-61-1)
• EPA Substance Registry System: N-(2,6-Diphenylmethyl)-1-piperazine acetylamine(5294-61-1)

Safety Data

• HazardClass: IRRITANT
• Hazardous Substances Data: 5294-61-1(Hazardous Substances Data)

Usage

Chemical Properties

Pale Beige Solid

InChI:InChI=1/C14H21N3O/c1-11-4-3-5-12(2)14(11)16-13(18)10-17-8-6-15-7-9-17/h3-5,15H,6-10H2,1-2H3,(H,16,18)/p+2

Synthetic route

2-chloro-N-(2,6-dimethylphenyl)acetamide (1131-01-7) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
In water at 80 - 110℃; for 7h;	95%

piperazine (110-85-0) + 2-chloro-N-(2,6-dimethylphenyl)acetamide (1131-01-7) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
With tetrabutyl ammonium fluoride In water at 20 - 60℃; for 3h;	85%
In ethanol at 80℃; for 3h; Product distribution / selectivity;	77%
In methanol at 25℃; Reflux; Large scale reaction;	71%

tert-butyl 4-(2-((2,6-dimethylphenyl)amino)-2-oxoethyl)piperazine-1-carboxylate (1324752-00-2) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 0℃; for 3h;	72%

piperazine (110-85-0) + formaldehyd (50-00-0) + 2,6-dimethylphenyl isonitrile (119072-54-7, 2769-71-3) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
With 2-(hydroxymethyl)benzoic acid In methanol Ugi Condensation; Reflux;	70%

piperazine hexahydrate (142-63-2) + 2-chloro-N-(2,6-dimethylphenyl)acetamide (1131-01-7) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
In ethanol for 3h; Reflux;	63%

piperazine (110-85-0) + 2-chloro-N-(2,6-dimethylphenyl)acetamide (1131-01-7) → 2,2'-(piperazine-1,4-diyl)bis(N-(2,6-dimethylphenyl)acetamide) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
In methanol at 25℃; Reflux; Large scale reaction;	A 34.6% B 21%
With hydrogenchloride In isopropyl alcohol at 80℃; for 21h; Inert atmosphere;
Stage #1: piperazine With hydrogenchloride In water at 10 - 30℃; Inert atmosphere; Large scale; Stage #2: 2-chloro-N-(2,6-dimethylphenyl)acetamide In water at 80℃; for 2h; Solvent; Time; Concentration; Inert atmosphere; Large scale;	A n/a B 5.12 kg
With sodium carbonate In tetrahydrofuran at 20℃; for 72h;

diisopropylamine (108-18-9) + 2-chloro-N-(2,6-dimethylphenyl)acetamide (1131-01-7) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
In ethanol

2-chloro-N-(2,6-dimethylphenyl)acetamide (1131-01-7) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol
With N-ethyl-N,N-diisopropylamine In ethanol
Multi-step reaction with 2 steps 1: triethylamine / acetonitrile / 4 h / 25 °C 2: trifluoroacetic acid / dichloromethane / 3 h / 0 °C View Scheme

2,6-dimethylaniline (87-62-7) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium carbonate / dichloromethane / 1.5 h / 10 - 15 °C / Large scale reaction 2: methanol / 25 °C / Reflux; Large scale reaction View Scheme
Multi-step reaction with 2 steps 1: sodium carbonate / dichloromethane / 1.5 h / 10 - 15 °C / Large scale reaction 2: methanol / 25 °C / Reflux; Large scale reaction View Scheme
Multi-step reaction with 2 steps 1: water / 2 h / 20 °C 2: water / 7 h / 80 - 110 °C View Scheme

piperazine monophosphate + 2-chloro-N-(2,6-dimethylphenyl)acetamide (1131-01-7) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
In water Reflux;

N-(2,6-dimethylphenyl)-4-formyl-1-piperazineacetamide (159484-66-9) → N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1)

Conditions	Yield
With sodium hydroxide In water at 80℃; for 8h; pH=10; Reagent/catalyst;

2-isothiocyanato-4,5-dimethoxybenzonitrile (43091-89-0) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 3,4-Dimethoxy-6-<4-(2,6-dimethylacetanilido)piperazin-1-yl>thiocarbamido-benzonitrile (122001-69-8)

Conditions	Yield
In ethyl acetate for 20h;	100%

(R)-(-)-epichlorohydrin (51594-55-9) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → (R)-2-(4-(3-chloro-2-hydroxypropyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide (1427177-24-9)

Conditions	Yield
In water at 15℃; for 1h;	97%

(S)-epichlorohydrin (67843-74-7) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → (S)-2-(4-(3-chloro-2-hydroxypropyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide (1427177-25-0)

Conditions	Yield
In water at 15℃; for 1h;	96%

1-chloromethyl-4-fluorobenzene (352-11-4) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → N-(2,6-dimethylphenyl)-2-(4-(4-fluorobenzyl)piperazin-1-yl)acetamide

Conditions	Yield
With potassium carbonate In acetonitrile at 25℃; for 10h;	94%

3,4-Dichlorophenylmethyl chloride (102-47-6) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 2-(4-(3,4-dichlorobenzyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide

Conditions	Yield
With potassium carbonate In acetonitrile at 25℃; for 10h;	93%

2-fluorobenzyl chloride (345-35-7) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → N-(2,6-dimethylphenyl)-2-(4-(2-fluorobenzyl)piperazin-1-yl)acetamide

Conditions	Yield
With potassium carbonate In acetonitrile at 25℃; for 10h;	93%

p-bromobenzyl chloride (589-17-3) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 2-(4-(4-bromobenzyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide

Conditions	Yield
With potassium carbonate In acetonitrile at 25℃; for 10h;	92%

2-chloro-6 fluorobenzyl chloride (55117-15-2) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 2-(4-(2-chloro-6-fluorobenzyl)piperazin-1-yl)-N-(2,6- dimethylphenyl)acetamide

Conditions	Yield
With potassium carbonate In acetonitrile at 25℃; for 10h;	91%

4-methoxy-phenyl-sulphonyl chloride (98-68-0) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → N-(2,6-dimethylphenyl)-2-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)acetamide

Conditions	Yield
With triethylamine In dichloromethane at 25℃; for 8h;	91%

2-(bromomethyl)benzonitrile (22115-41-9) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → N-(2,6-dimethylphenyl)-2-[4-(2-cyanobenzyl)piperazin-1-yl]acetamide (185407-95-8)

Conditions	Yield
With triethylamine In toluene for 3h; Heating;	90%

4-chlorobenzenesulfonyl chloride (98-60-2) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 2-(4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide

Conditions	Yield
With triethylamine In dichloromethane at 25℃; for 8h;	90%

4-bromobenzenesulfonyl chloride (98-58-8) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 2-(4-((4-bromophenyl)sulfonyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide

Conditions	Yield
With triethylamine In dichloromethane at 25℃; for 8h;	90%

4-Nitrobenzenesulfonyl chloride (98-74-8) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → N-(2,6-dimethylphenyl)-2-(4-((4-nitrophenyl)sulfonyl)piperazin-1-yl)acetamide

Conditions	Yield
With triethylamine In dichloromethane at 25℃; for 8h;	89%

N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) + 1-bromo-3-(2-methoxyphenoxy)-2-propyl alcohol → Ranolazine (95635-55-5)

Conditions	Yield
With potassium carbonate In ethanol; toluene for 3h; Solvent; Reagent/catalyst; Time; Temperature; Reflux;	87.4%

p-toluenesulfonyl chloride (98-59-9) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → N-(2,6-dimethylphenyl)-2-(4-tosylpiperazin-1-yl)acetamide

Conditions	Yield
With triethylamine In dichloromethane at 25℃; for 8h;	87%

3-(bromomethyl)benzonitrile (28188-41-2) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → N-(2,6-dimethylphenyl)-2-[4-(3-cyanobenzyl)piperazin-1-yl]acetamide (185407-96-9)

Conditions	Yield
With triethylamine In toluene for 3h; Heating;	85%

2-(2-methoxy-phenoxymethyl)-oxirane (2210-74-4) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → Ranolazine (95635-55-5)

Conditions	Yield
With Sulfated tungstate at 70℃; for 2h; Green chemistry;	85%
In methanol at 60℃; for 5h; Solvent;	85%
In methanol; toluene at 65℃; for 9h;	69.8%

benzonitrile (100-47-0) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 2-(4-benzylpiperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide (55340-20-0)

Conditions	Yield
With borane-ammonia complex; C16H29Cl2CoN2P at 20℃; for 13h; Schlenk technique; Inert atmosphere; chemoselective reaction;	82%

1-chloro-3-(2-methoxyphenoxy)-2-propyl alcohol (25772-81-0) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → Ranolazine (95635-55-5)

Conditions	Yield
With potassium carbonate In methanol; toluene for 4.5h; Solvent; Reagent/catalyst; Temperature; Reflux;	80.1%

1-(2-benzyloxyphenoxy)-2,3-propylene oxide (22530-53-6) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 1-[3-(2-benzyloxyphenoxy)-2-hydroxypropyl]-4-[N-(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine (1209000-03-2)

Conditions	Yield
In methanol; toluene at 65℃; for 9h;	74.7%

epichlorohydrin (106-89-8) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → (RS)-2-(4-(3-chloro-2-hydroxyphenyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide (1427177-23-8)

Conditions	Yield
With palladium on activated charcoal In water at 20℃; for 2h;	72.8%
With sodium dodecyl-sulfate In water at 15℃; for 12h; Green chemistry;	70%
In water at 15℃; for 1h;

1-(4-methoxy-2-(ethylene oxide-2-ylmethoxy)phenyl)ethanone (49645-95-6) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 2-(4-(3-(2-acetyl-5-methoxyphenoxy)-2-hydroxypropyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide

Conditions	Yield
In ethanol at 20℃;	72.4%

2-chloro-6,7-dimethoxyquinazolin-4-amine (23680-84-4) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 2-<4-(2,6-Dimethylacetanilide)piperazin-1-yl>-4-amino-6,7-dimethoxyquinazoline hydrochloride

Conditions	Yield
In i-Amyl alcohol for 2.5h; Heating;	70%

3-monochloro-1,2-propanediol (96-24-2) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → CVT-2512

Conditions	Yield
With sodium hydrogencarbonate In ethanol at 65℃;	66.2%

epichlorohydrin (106-89-8) + N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (5294-61-1) → 1,3-bis{4-[(2,6-dimethylphenyl)aminocarbonylmethyl]-piperazin-1-yl}propan-2-ol (1213269-66-9)

Conditions	Yield
In acetone for 15h; Reflux;	45%

Upstream product

• 1324752-00-2 tert-butyl 4-(2-((2,6-dimethylphenyl)amino)-2-oxoethyl)piperazine-1-carboxylate 
• 1131-01-7 2-chloro-N-(2,6-dimethylphenyl)acetamide 
• 142-63-2 piperazine hexahydrate 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 110-85-0 piperazine 
• 50-00-0 formaldehyd 
• 119072-54-7 2,6-dimethylphenyl isonitrile 
• 87-62-7 2,6-dimethylaniline 
• 108-18-9 diisopropylamine 
• 159484-66-9 N-(2,6-dimethylphenyl)-4-formyl-1-piperazineacetamide 

Downstream Products

• 95635-55-5 Ranolazine 
• 1213269-66-9 1,3-bis{4-[(2,6-dimethylphenyl)aminocarbonylmethyl]-piperazin-1-yl}propan-2-ol 
• 1427177-23-8 (RS)-2-(4-(3-chloro-2-hydroxyphenyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide 
• 1427177-24-9 (R)-2-(4-(3-chloro-2-hydroxypropyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide 
• 1427177-25-0 (S)-2-(4-(3-chloro-2-hydroxypropyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide 
• 142387-99-3 (R)-Ranolazine 
• 114246-81-0 (S)-Ranolazine 

Relevant articles and documents

Benzyl and sulfonyl derivatives of n-(2,6-dimethylphenyl)-2(piperazin-1-yl)acetamide (t2288): biological screening and fingerprint applications

A series of five N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide (T2288) sulfonamides 6a-e and its five alkylated piperazine derivatives 8a-e have been synthesized, characterized and screened for antibacterial, antifungal and anthelmintic activity. Some of the compounds showed significant biological activities. Molecular docking to crystal structures of target proteins revealed that, active compounds show similar binding poses as that of standards, indicating good correlation of the binding energy with observed in vitro data for the active compounds. Finally, the study of latent fingerprint analysis showed that the compound 6c exhibits good stickiness and finger rhythm without dense dust. The resulting compound can be used to detect fingerprints on all types of flat surfaces and hence easily accepted for detecting hidden fingerprints. This research can offer an excellent setting that can lead to the discovery of potential antibacterial, antifungal, anthelmintic and fingerprint agents.

NOVEL PROCESS FOR THE PREPARATION OF RANOLAZINE

The present invention relates to novel processes for the preparation of Ranolazine (I) and its acid addition salts and the novel process for the preparation of compound of formula (7).

COMPOSITIONS AND METHODS FOR THE TREATMENT ANGINA AND CARDIOVASCULAR CONDITIONS

The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of angina and cardiovascular conditions may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of chronic aneurysm, angina, atherosclerosis, cerebrovascular accident (stroke), cerebrovascular disease, congestive heart failure, coronary artery disease, myocardial infarction (heart attack), peripheral vascular disease, aortic dissection, aortic stenosis, arrhythmia (irregular heartbeat), atrial fibrillation, cardiomyopathy, chest pain, claudication, congenital heart disease.